However four unanswered goals; two at the start and two at the end of the third period from the Phoenix kept alive their hopes of progressing to the semi-finals.
The Phoenix took the honours in an even first period as both netminders faced 13 shots each as they netted the only goal at 13.02 with a Nathan Ward (first) strike.
The Phoenix doubled their lead 65 seconds into the second period with a goal from Luke Fulgham (second).
The Vipers quickly replied to this set back as less than two minutes later Rob Rankin (second) pulled one back at 23.02, tipping in Chris McAllister's blueline wristshot.
They were then back on level terms at 26.24 with an almost identical counter from Tyler Willis (second), deflecting Rob Wilson's effort past Stephen Murphy.
Just over half way Vipers player/coach Rob Wilson took a penalty for interference and the Phoenix took the initiative on the powerplay to regain the lead as Alex Dunn (fourth) scored at 31.52.
Two goals inside a minute gave the Phoenix a three goal lead at the start of the third period.
Brett Clouthier (first) at 42.07 was followed by a strike by David Beauregard (tenth) at 42.59.
A further two goal from the Phoenix late in the game sealed the win, as Luke Fulgham (third), below left, with his second of the game at 57.56 found the empty net after Vipers had pulled the goalie and then Adam Walker (second) on the powerplay at 59.45 completed a good night's work for the Phoenix.
Period Scores: 0-1, 2-2, 0-4
Penalty Mins: 18-10
Powerplay: New 0/2 - Man 2/6
Shots On: Andrew Verner 40 + 1 ENG – Stephen Murphy 31.
Rob Wilson watched his Vipers side lose their opening Challenge Cup match to Manchester, and told
newcastlevipers.com that too many individual mistakes led to Manchester goals.
"Last night in Cardiff I felt we were a match for any team, and it was one of our better performances.
"Tonight I think there was a little hangover from that, getting back at 5-6 this morning then having the early start here tonight.
"That said, there were individual mistakes which cost us, and Manchester capitalised.
"I've told the players that we are better than what we've shown tonight, and we will be working all week in practice to put things right."
It is symptomatic of this season that the Vipers followed up one of their best performances – Saturday's 2-1 over-time success in Cardiff – with one of their worst. Wilson, though, remains defiant.
"I'm not counting us out of anything right now. The Challenge Cup will be difficult to qualify but certainly not impossible.
"It makes next Sunday's game against Edinburgh a must-win, and then we have to get points from both Sheffield and Belfast.
"It's not easy, but when have the Vipers ever done anything the easy way?"
The Mincoffs-backed Vipers are in league action on Saturday night away to Basingstoke Bison before their last home Challenge Cup match against Edinburgh 24 hours later.
The cup game is once again at Whitley's Hillheads rink, with a later-than-usual 7pm face-off.
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